A comparative view on mechanisms and functions of skeletal remodelling in teleost fish, with special emphasis on osteoclasts and their function

Abstract

Resorption and remodelling of skeletal tissues is required for development and growth, mechanical adaptation, repair, and mineral homeostasis of the vertebrate skeleton. Here we review for the first time the current knowledge about resorption and remodelling of the skeleton in teleost fish, the largest and most diverse group of extant vertebrates. Teleost species are increasingly used in aquaculture and as models in biomedical skeletal research. Thus, detailed knowledge is required to establish the differences and similarities between mammalian and teleost skeletal remodelling, and between distantly related species such as zebrafish (Danio rerio) and medaka (Oryzias latipes). The cellular mechanisms of differentiation and activation of osteoclasts and the functions of teleost skeletal remodelling are described. Several characteristics, related to skeletal remodelling, distinguish teleosts from mammals. These characteristics include (a) the absence of osteocytes in most species; (b) the absence of haematopoietic bone marrow tissue; (c) the abundance of small mononucleated osteoclasts performing non-lacunar (smooth) bone resorption, in addition to or instead of multinucleated osteoclasts; and (d) a phosphorus- rather than calcium-driven mineral homeostasis (mainly affecting the postcranial dermal skeleton). Furthermore, (e) skeletal resorption is often absent from particular sites, due to sparse or lacking endochondral ossification. Based on the mode of skeletal remodelling in early ontogeny of all teleosts and in later stages of development of teleosts with acellular bone we suggest a link between acellular bone and the predominance of mononucleated osteoclasts, on the one hand, and cellular bone and multinucleated osteoclasts on the other. The evolutionary origin of skeletal remodelling is discussed and whether mononucleated osteoclasts represent an ancestral type of resorbing cells. Revealing the differentiation and activation of teleost skeletal resorbing cells, in the absence of several factors that trigger mammalian osteoclast differentiation, is a current challenge. Understanding which characters of teleost bone remodelling are derived and which characters are conserved should enhance our understanding of the process in fish and may provide insights into alternative pathways of bone remodelling in mammals.

The enigmas of bone without osteocytes

“…Similarly, Kilhara et al 47 showed that lordosis can be induced in juvenile red sea bream (Pragus major) by increased swimming activity. Bone modeling was also demonstrated by Meyer, 48 Huysseune et al, 49 Hegrenes, 50 Witten and Huysseune, 33 and Muschick et al 51 who showed adaptive changes in the pharyngeal jaw bones of cichlids (Astatoreochromis alluaudi and Amphilophus spp.) in the form of gross reshaping of the jaws and thickening/ reorientation of internal trabeculae, in response to increased mechanical load caused by being fed a harder diet.…”

“…88 Fortunately, fish rarely encounter this circumstance, as calcium is plentiful in both sea and fresh water, and thus is a readily available reservoir during times of demand. 33 It was furthermore demonstrated that if calcium deficiency is imposed on fishes artificially, they will preferentially mobilize calcium stores by resorbing their scales (exoskeleton) rather than the bones of the endoskeleton. 87 In fact, it has been shown that the more common cause for bone resorption in fish is phosphorous deficiency.…”

“…29 In fact, the lack of osteocytes (as well as the lacunocanalicular spaces) is the only fundamental difference between the bones of the majority of teleost fish species (particularly the more derived ones) and those of all tetrapods. 26,[30][31][32][33] The fact that there are many extant taxa of osteocytic ('cellular') boned fishes, offers a fantastic palette for comparing the role of bone cells in acellular and cellular bone, but also for investigating the effects of osteocyte loss on a phylogenetic scale (especially since acellularity evolved independently several times within fishes). 34 The evolution of acellular bone from cellular-boned ancestors, and the dominance of this character in advanced teleosts raise the intriguing possibility that a lack of osteocytes brings some functional advantage.…”

“…The proposed hypothesis, 33 that osteoblasts are involved in mechanosensing in acellular bone, is supported by Kitamura et al's 76 demonstration in the (acellular and dermal) scales of goldfish of increased osteoblast but not osteoclast activity (via alkaline phosphatase (ALP) and tartarate resistant acid phosphatase (TRAP) staining, respectively) in response to increased swimming activity, and by in vitro studies of mammalian mesenchymal tissue-derived cells at various stages of differentiation showing response to their mechanical environment. [77][78][79][80][81] Lu et al's 55 illustration in vitro of higher mechanosensitivity in mammalian osteocytes than osteoblasts, however, suggests perhaps a different level of osteoblast mechanosensitivity in fish bone, starkly different loading demands, bone material properties in fishes and mammals, and/or recruitment of other mechanosensors in addition to Bone without osteocytes R Shahar and MN Dean osteoblasts.…”

“…87 In fact, it has been shown that the more common cause for bone resorption in fish is phosphorous deficiency. 33,89,90 Phosphorus is an essential mineral for fish, needed for bone mineralization as well as for various metabolic pathways. However, as opposed to calcium, its availability in both fresh water and seawater is relatively low, and adequate levels depend on dietary intake.…”